RecQ helicases are a family of highly conserved proteins that maintain genomic stability through their important roles in replication restart mechanisms. Cellular phenotypes of RECQ1 deficiency are indicative of aberrant repair of stalled replication forks, but the molecular functions of RECQ1, the most abundant of the five known human RecQ homologues, have remained poorly understood. We show that RECQ1 associates with FEN-1 (flap endonuclease-1) in nuclear extracts and exhibits direct protein interaction in vitro. Recombinant RECQ1 significantly stimulated FEN-1 endonucleolytic cleavage of 5′-flap DNA substrates containing non-telomeric or telomeric repeat sequence. RECQ1 and FEN-1 were constitutively present at telomeres and their binding to the telomeric chromatin was enhanced following DNA damage. Telomere residence of FEN-1 was dependent on RECQ1 since depletion of RECQ1 reduced FEN-1 binding to telomeres in unperturbed cycling cells. Our results confirm a conserved collaboration of human RecQ helicases with FEN-1 and suggest both overlapping and specialized roles of RECQ1 in the processing of DNA structure intermediates proposed to arise during replication, repair and recombination.
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Research Article|
May 22 2015
RECQ1 interacts with FEN-1 and promotes binding of FEN-1 to telomeric chromatin Available to Purchase
Furqan Sami;
Furqan Sami
*Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, 520 W Street NW, Washington, DC 20059, U.S.A.
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Xing Lu;
Xing Lu
*Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, 520 W Street NW, Washington, DC 20059, U.S.A.
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Swetha Parvathaneni;
Swetha Parvathaneni
*Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, 520 W Street NW, Washington, DC 20059, U.S.A.
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Rabindra Roy;
Rabindra Roy
†Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3800 Reservoir Road NW, Washington, DC 20057, U.S.A.
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Ronald K. Gary;
Ronald K. Gary
‡Department of Chemistry, University of Nevada, Las Vegas 4505 Maryland Parkway, Las Vegas, NV 89154-4003, U.S.A.
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Sudha Sharma
Sudha Sharma
1
*Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, 520 W Street NW, Washington, DC 20059, U.S.A.
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
August 07 2014
Revision Received:
March 09 2015
Accepted:
March 16 2015
Accepted Manuscript online:
March 16 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2015 Biochemical Society
2015
Biochem J (2015) 468 (2): 227–244.
Article history
Received:
August 07 2014
Revision Received:
March 09 2015
Accepted:
March 16 2015
Accepted Manuscript online:
March 16 2015
Citation
Furqan Sami, Xing Lu, Swetha Parvathaneni, Rabindra Roy, Ronald K. Gary, Sudha Sharma; RECQ1 interacts with FEN-1 and promotes binding of FEN-1 to telomeric chromatin. Biochem J 1 June 2015; 468 (2): 227–244. doi: https://doi.org/10.1042/BJ20141021
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